Moorman J R, Kirsch G E, Lacerda A E, Brown A M
Department of Medicine, University of Texas Medical Branch, Galveston 77550.
Circ Res. 1989 Dec;65(6):1804-9. doi: 10.1161/01.res.65.6.1804.
Since chronic congestive heart failure syndromes are associated with both elevated circulating levels of angiotensin II and potentially lethal ventricular tachyarrhythmias, we investigated the effect of angiotensin II on voltage-dependent cardiac Na+ currents. Single-channel Na+ currents in neonatal rat ventricular myocytes were studied using the patch clamp method in the cell-attached mode. Angiotensin II applied outside the patch increased the frequency of opening and rates of activation and inactivation of single-channel Na+ currents within the patch. These effects were mimicked by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and were prevented by prior incubation with TPA. Therefore, we propose that angiotensin II modulates cardiac Na+ currents by a cytoplasmic second messenger, perhaps protein kinase C, and this may predispose toward arrhythmia.
由于慢性充血性心力衰竭综合征与血管紧张素II循环水平升高和潜在致命的室性快速性心律失常均有关联，我们研究了血管紧张素II对电压依赖性心脏钠电流的影响。采用膜片钳技术的细胞贴附模式，研究新生大鼠心室肌细胞中的单通道钠电流。施加于膜片外部的血管紧张素II增加了膜片内单通道钠电流的开放频率、激活速率和失活速率。佛波酯12-O-十四酰佛波醇-13-乙酸酯（TPA）可模拟这些效应，且预先用TPA孵育可阻止这些效应。因此，我们提出血管紧张素II通过一种胞质第二信使（可能是蛋白激酶C）来调节心脏钠电流，这可能易导致心律失常。
